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The Influence of Tissue Specific Cardiac and Skeletal Muscle Extracellular Matrix on Muscle Remodeling

Wolf, Matthew (2014) The Influence of Tissue Specific Cardiac and Skeletal Muscle Extracellular Matrix on Muscle Remodeling. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Volumetric muscle loss (VML) in skeletal muscle and loss of cardiac function after myocardial infarction lack viable treatment options for functional tissue restoration. Previously investigated strategies such as synthetic graft placement and cell therapy are limited in their ability to restore function to these tissues. Biologic scaffolds composed of extracellular matrix (ECM) have been prepared from numerous source tissues including small intestine, urinary bladder, liver, and dermis. When properly prepared, ECM scaffolds implanted into a site of injury are rapidly infiltrated by host cells, subjected to degradation, and often remodel into site appropriate host tissue. The ECM of tissues and organs represents the secreted products of resident cells, a process which provides a unique microenvironmental niche that influences cell behavior during homeostasis and injury. The objective of the present study was to develop and characterize muscle tissue specific scaffolds composed of skeletal (M-ECM) and cardiac muscle (C-ECM), and to determine whether a muscle tissue ECM scaffold preferentially promotes muscle restoration compared to non-muscle ECM.
A method of skeletal and cardiac muscle decellularization was developed that efficiently removed cells while preserving native ECM components, including basement membrane proteins, glycosaminoglycans, and growth factors. Degradation products produced by pepsin digestion of M-ECM, C-ECM, and non-muscle ECM derived from small intestinal submucosa (SIS-ECM) decreased proliferation and promoted the myogenic differentiation of perivascular stem cells in vitro. Although M-ECM was more rapidly degraded than both C-ECM and SIS ECM, all ECM scaffolds showed a similar increase in functional skeletal myogenesis.
These studies show that M-ECM and C-ECM can be prepared in a manner that preserves muscle ECM specific components and biologic activity. M-ECM promoted stem cell myogenic activity in a non-tissue specific manner in vitro, and both muscle and non-muscle ECM promoted functional myogenesis to a similar extent in vivo. These results indicate that M-ECM is not a preferred substrate for skeletal muscle remodeling compared to C-ECM and SIS-ECM.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Wolf, Matthewmtw16@pitt.eduMTW16
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorBadylak, Stephen
Committee MemberWagner, William R.wagnerwr@upmc.eduWAGNER
Committee MemberShroff, Sanjeev G.sshroff@pitt.eduSSHROFF
Committee MemberAmbrosio,
Committee MemberWeber, Douglas J.djw50@pitt.eduDJW50
Date: 16 June 2014
Date Type: Publication
Defense Date: 19 December 2013
Approval Date: 16 June 2014
Submission Date: 31 March 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 179
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Extracellular matrix, biologic scaffold, skeletal muscle, cardiac muscle, regenerative medicine
Date Deposited: 16 Jun 2014 18:49
Last Modified: 19 Dec 2016 14:41


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